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Ivermectin (, '' EYE-vər-MEK-tin'') is an
antiparasitic Antiparasitics are a class of medications which are indicated for the treatment of parasitic diseases, such as those caused by helminths, amoeba, ectoparasites, parasitic fungi, and protozoa, among others. Antiparasitics target the parasitic agent ...
drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...
. After its discovery in 1975, its first uses were in veterinary medicine to prevent and treat
heartworm ''Dirofilaria immitis'', also known as heartworm or dog heartworm, is a parasitic roundworm that is a type of filarial worm, a small thread-like worm, that causes dirofilariasis. It is spread from host to host through the bites of mosquitoe ...
and
acariasis Acariasis is an infestation with mites. Terminology There are several complications with the terminology: Acariasis is a term for a rash, caused by mites, sometimes with a papillae (pruritic dermatitis) or papule (papular urticaria), and usua ...
. Approved for human use in 1987, today it is used to treat infestations including
head lice The head louse (''Pediculus humanus capitis'') is an obligate ectoparasite of humans. Head lice are wingless insects that spend their entire lives on the human scalp and feeding exclusively on human blood. Humans are the only known hosts of thi ...
,
scabies Scabies (; also sometimes known as the seven-year itch) is a contagious skin infestation by the mite ''Sarcoptes scabiei''. The most common symptoms are severe itchiness and a pimple-like rash. Occasionally, tiny burrows may appear on the skin ...
,
river blindness Onchocerciasis, also known as river blindness, is a disease caused by infection with the parasitic worm ''Onchocerca volvulus''. Symptoms include severe itching, bumps under the skin, and blindness. It is the second-most common cause of blindne ...
(onchocerciasis),
strongyloidiasis Strongyloidiasis is a human parasitic disease caused by the nematode called '' Strongyloides stercoralis'', or sometimes the closely related ''S. fülleborni''. These helminths belong to a group of nematodes called roundworms. These intestinal wo ...
,
trichuriasis Trichuriasis, also known as whipworm infection, is an infection by the parasitic worm ''Trichuris trichiura'' (whipworm). If infection is only with a few worms, there are often no symptoms. In those who are infected with many worms, there may b ...
,
ascariasis Ascariasis is a disease caused by the parasitic roundworm ''Ascaris lumbricoides''. Infections have no symptoms in more than 85% of cases, especially if the number of worms is small. Symptoms increase with the number of worms present and may in ...
and
lymphatic filariasis Lymphatic filariasis is a human disease caused by parasitic worms known as filarial worms. Usually acquired in childhood, it is a leading cause of permanent disability worldwide. While most cases have no symptoms, some people develop a syndrome ...
. It works through many mechanisms to kill the targeted parasites, and can be taken orally, or applied to the skin for external infestations. It belongs to the
avermectin The avermectins are a series of drugs and pesticides used to treat parasitic worms and insect pests. They are a group of 16-membered macrocyclic lactone derivatives with potent anthelmintic and insecticidal properties. These naturally occurring c ...
family of medications. William Campbell and
Satoshi Ōmura is a Japanese biochemist. He is known for the discovery and development of hundreds of pharmaceuticals originally occurring in microorganisms. In 2015, he was awarded the Nobel Prize in Physiology or Medicine jointly with William C. Campbell fo ...
won the 2015
Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
for its discovery and applications. It is on the
World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...
, and is approved by the U.S.
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
as an
antiparasitic agent Antiparasitics are a class of medications which are indicated for the treatment of parasitic diseases, such as those caused by helminths, amoeba, ectoparasites, parasitic fungi, and protozoa, among others. Antiparasitics target the parasitic agent ...
. In 2018, it was the 420th most commonly prescribed medication in the United States, with more than 100,000 prescriptions. It is available as a
generic medicine A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...
. During the
COVID-19 pandemic The COVID-19 pandemic, also known as the coronavirus pandemic, is an ongoing global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The novel virus was first identif ...
,
misinformation Misinformation is incorrect or misleading information. It differs from disinformation, which is ''deliberately'' deceptive. Rumors are information not attributed to any particular source, and so are unreliable and often unverified, but can turn ou ...
has been widely spread claiming that ivermectin is beneficial for treating and preventing
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was COVID-19 pandemic in Hubei, identified in Wuhan, China, in December ...
. Such claims are not backed by credible scientific evidence. Multiple major health organizations, including the Food and Drug Administration, U.S.
Centers for Disease Control The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
, the
European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...
, and the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
have stated that ivermectin is not authorized or approved to treat COVID-19.


Medical uses

Ivermectin is used to treat human diseases caused by
roundworm The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant-parasitic nematodes also known as eelworms. They are a diverse animal phylum inhabiting a bro ...
s and a wide variety of external parasites.


Worm infections

For
river blindness Onchocerciasis, also known as river blindness, is a disease caused by infection with the parasitic worm ''Onchocerca volvulus''. Symptoms include severe itching, bumps under the skin, and blindness. It is the second-most common cause of blindne ...
(onchocerciasis) and
lymphatic filariasis Lymphatic filariasis is a human disease caused by parasitic worms known as filarial worms. Usually acquired in childhood, it is a leading cause of permanent disability worldwide. While most cases have no symptoms, some people develop a syndrome ...
, ivermectin is typically given as part of
mass drug administration The administration of drugs to whole populations irrespective of disease status is referred to as mass drug administration (MDA). This article describes the administration of antimalarial drugs to whole populations an intervention which has been u ...
campaigns that distribute the drug to all members of a community affected by the disease. For river blindness, a single oral dose of ivermectin (150
microgram In the metric system, a microgram or microgramme is a unit of mass equal to one millionth () of a gram. The unit symbol is μg according to the International System of Units (SI); the recommended symbol in the United States and United Kingdom whe ...
s per kilogram of body weight) clears the body of larval ''
Onchocerca volvulus ''Onchocerca volvulus'' is a filarial (arthropod-borne) nematode (roundworm) that causes onchocerciasis (river blindness), and is the second-leading cause of blindness due to infection worldwide after trachoma. It is one of the 20 neglected trop ...
'' worms for several months, preventing transmission and disease progression. Adult worms survive in the skin and eventually recover to produce larval worms again; to keep the worms at bay, ivermectin is given at least once per year for the 1015-year lifespan of the adult worms. For
lymphatic filariasis Lymphatic filariasis is a human disease caused by parasitic worms known as filarial worms. Usually acquired in childhood, it is a leading cause of permanent disability worldwide. While most cases have no symptoms, some people develop a syndrome ...
, oral ivermectin (200 micrograms per kilogram body weight) is part of a combination treatment given annually: ivermectin, diethylcarbamazine citrate and
albendazole Albendazole (also known as albendazolum) is a broad-spectrum anthelmintic and antiprotozoal agent of the benzimidazole type. It is used for the treatment of a variety of intestinal parasite infections, including ascariasis, pinworm infection, h ...
in places without onchocerciasis; and ivermectin and albendazole in places with onchocerciasis. The
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
(WHO) considers ivermectin the drug of choice for
strongyloidiasis Strongyloidiasis is a human parasitic disease caused by the nematode called '' Strongyloides stercoralis'', or sometimes the closely related ''S. fülleborni''. These helminths belong to a group of nematodes called roundworms. These intestinal wo ...
. Most cases are treated with two daily doses of oral ivermectin (200 μg per kg body weight), while severe infections are treated with five to seven days of ivermectin. Ivermectin is also the primary treatment for '' Mansonella ozzardi'' and
cutaneous larva migrans Cutaneous larva migrans (abbreviated CLM) is a skin disease in humans, caused by the larvae of various nematode parasites of the hookworm family (Ancylostomatidae). These parasites live in the intestines of dogs, cats, and wild animals and should ...
. The U.S.
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
(CDC) recommends ivermectin, albendazole, or
mebendazole Mebendazole (MBZ), sold under the brand name Vermox among others, is a medication used to treat a number of parasitic worm infestations. This includes ascariasis, pinworm infection, hookworm infections, guinea worm infections, hydatid disea ...
as treatments for
ascariasis Ascariasis is a disease caused by the parasitic roundworm ''Ascaris lumbricoides''. Infections have no symptoms in more than 85% of cases, especially if the number of worms is small. Symptoms increase with the number of worms present and may in ...
. Ivermectin is sometimes added to albendazole or mebendazole for
whipworm ''Trichuris trichiura, Trichocephalus trichiuris'' or whipworm, is a parasitic roundworm (a type of helminth) that causes trichuriasis (a type of helminthiasis which is one of the neglected tropical diseases) when it infects a human large intes ...
treatment, and is considered a second-line treatment for
gnathostomiasis Gnathostomiasis (also known as larva migrans profundus) is the human infection caused by the nematode (roundworm) ''Gnathostoma spinigerum'' and/or '' Gnathostoma hispidum'', which infects vertebrates. Symptoms and signs A few days after ingestio ...
.


Mites and insects

Ivermectin is also used to treat infection with parasitic arthropods.
Scabies Scabies (; also sometimes known as the seven-year itch) is a contagious skin infestation by the mite ''Sarcoptes scabiei''. The most common symptoms are severe itchiness and a pimple-like rash. Occasionally, tiny burrows may appear on the skin ...
– infestation with the mite ''
Sarcoptes scabiei ''Sarcoptes scabiei'' or the itch mite is a parasitic mite that burrows into skin and causes scabies. The mite is found in all parts of the world. Humans are not the only mammals that can become infected. Other mammals, such as wild and domesti ...
'' – is most commonly treated with topical
permethrin Permethrin is a medication and an insecticide. As a medication, it is used to treat scabies and lice. It is applied to the skin as a cream or lotion. As an insecticide, it can be sprayed onto clothing or mosquito nets to kill the insects th ...
or oral ivermectin. A single application of permethrin is more efficacious than a single treatment of ivermectin. For most scabies cases, ivermectin is used in a two dose regimen: a first dose kills the active mites, but not their eggs. Over the next week, the eggs hatch, and a second dose kills the newly hatched mites. The two dose regimen of ivermectin has similar efficacy to the single dose permethrin treatment. Ivermectin is, however, more effective than permethrin when used in the mass treatment of endemic scabies. For severe "crusted scabies", where the parasite burden is orders of magnitude higher than usual, the U.S.
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
(CDC) recommends up to seven doses of ivermectin over the course of a month, along with a topical antiparasitic. Both
head lice The head louse (''Pediculus humanus capitis'') is an obligate ectoparasite of humans. Head lice are wingless insects that spend their entire lives on the human scalp and feeding exclusively on human blood. Humans are the only known hosts of thi ...
and
pubic lice Pediculosis pubis (also known as "crabs" and "pubic lice") is an infestation by the pubic louse, ''Pthirus pubis'', a wingless insect which feeds on blood and lays its eggs (nits) on mainly pubic hair. Less commonly, hair near the anus, armp ...
can be treated with oral ivermectin, an ivermectin lotion applied directly to the affected area, or various other insecticides. Ivermectin is also used to treat
rosacea Rosacea is a long-term skin condition that typically affects the face. It results in redness, pimples, swelling, and small and superficial dilated blood vessels. Often, the nose, cheeks, forehead, and chin are most involved. A red, enlarg ...
and blepharitis, both of which can be caused or exacerbated by ''
Demodex folliculorum ''Demodex folliculorum'' is a microscopic mite that can only survive on the skin of humans. Most people have ''D.folliculorum'' on their skin. Usually, the mites do not cause any harm, so are considered an example of commensalism rather than par ...
'' mites.


Contraindications

The only absolute contraindication to the use of ivermectin is hypersensitivity to the active ingredient or any component of the formulation. In children under the age of five or those who weigh less than , there is limited data regarding the efficacy or safety of ivermectin, though the available data demonstrate few adverse effects. However, the
American Academy of Pediatrics The American Academy of Pediatrics (AAP) is an American professional association of pediatricians, headquartered in Itasca, Illinois. It maintains its Department of Federal Affairs office in Washington, D.C. Background The Academy was founded ...
cautions against use of ivermectin in such patients, as the blood-brain barrier is less developed, and thus there may be an increased risk of particular CNS side effects such as encephalopathy, ataxia, coma, or death. Such patients should be monitored very closely when given ivermectin. The
American Academy of Family Physicians The American Academy of Family Physicians (AAFP) was founded in 1947 to promote and maintain high-quality standards for family medicine, an offshoot of the classical general practitioner. It is headquartered in Leawood, Kansas. AAFP is one of ...
also recommends against use in these patients, given a lack of sufficient data to prove drug safety. Ivermectin is secreted in very low concentration in breast milk. It remains unclear if ivermectin is safe during pregnancy.


Adverse effects

Side effects, although uncommon, include fever, itching, and skin rash when taken by mouth; and red eyes, dry skin, and burning skin when used topically for head lice. It is unclear if the drug is safe for use during
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
, but it is probably acceptable for use during
breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...
. Ivermectin is considered relatively free of toxicity in standard doses (around 300 µg/kg). Based on the data drug safety sheet for ivermectin, side effects are uncommon. However, serious adverse events following ivermectin treatment are more common in people with very high burdens of larval ''
Loa loa ''Loa loa'' is a filarial (arthropod-borne) nematode (roundworm) that causes ''Loa loa'' filariasis. ''Loa loa'' actually means "worm worm", but is commonly known as the "eye worm", as it localizes to the conjunctiva of the eye. ''Loa loa'' is ...
'' worms in their blood. Those who have over 30,000 microfilaria per
milliliter The litre (international spelling) or liter (American English spelling) (SI symbols L and l, other symbol used: ℓ) is a metric unit of volume. It is equal to 1 cubic decimetre (dm3), 1000 cubic centimetres (cm3) or 0.001 cubic metre (m3). ...
of blood risk inflammation and capillary blockage due to the rapid death of the microfilaria following ivermectin treatment. One concern is neurotoxicity after large overdoses, which in most mammalian species may manifest as
central nervous system depression Central nervous system (CNS) depression is a physiological state that can result in a decreased rate of breathing, decreased heart rate, and loss of consciousness possibly leading to coma or death. It is the result of inhibited or suppressed brai ...
,
ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...
, coma, and even death, as might be expected from potentiation of inhibitory chloride channels. Since drugs that inhibit the enzyme
CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...
often also inhibit P-glycoprotein transport, the risk of increased absorption past the blood-brain barrier exists when ivermectin is administered along with other CYP3A4 inhibitors. These drugs include
statin Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs. Low- ...
s,
HIV protease inhibitors Protease inhibitors (PIs) are medications that act by interfering with enzymes that cleave proteins. Some of the most well known are antiviral drugs widely used to treat HIV/AIDS and hepatitis C. These protease inhibitors prevent viral replicat ...
, many
calcium channel blocker Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...
s,
lidocaine Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. When used for local anaesthesia or in nerve blocks, lidoca ...
, the
benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...
s, and
glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...
s such as
dexamethasone Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena cav ...
. During the course of a typical treatment, ivermectin can cause minor aminotransferase elevations. In rare cases it can cause mild clinically apparent
liver disease Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Signs and symptoms Some of the sig ...
. To provide context for the dosing and toxicity ranges, the of ivermectin in mice is 25 mg/kg (oral), and 80 mg/kg in dogs, corresponding to an approximated human-equivalent dose LD50 range of 2.02-43.24 mg/kg, which is far in excess of its FDA-approved usage (a single dose of 0.150-0.200 mg/kg to be used for specific parasitic infections). While ivermectin has also been studied for use in COVID-19, and while it has some ability to inhibit SARS-CoV-2 in vitro, achieving 50% inhibition in vitro was found to require an estimated oral dose of 7.0 mg/kg (or 35x the maximum FDA-approved dosage), high enough to be considered ivermectin poisoning. Despite insufficient data to show any safe and effective dosing regimen for ivermectin in COVID-19, doses have been taken far in excess of FDA-approved dosing, leading the CDC to issue a warning of overdose symptoms including nausea, vomiting, diarrhea, hypotension,
decreased level of consciousness An altered level of consciousness is any measure of arousal other than normal. Level of consciousness (LOC) is a measurement of a person's arousability and responsiveness to stimuli from the environment. A mildly depressed level of consciousne ...
, confusion, blurred vision, visual hallucinations, loss of coordination and balance, seizures, coma, and death. The CDC advises against consuming doses intended for livestock or doses intended for external use and warns that increasing misuse of ivermectin-containing products is resulting in an increasing rate of harmful overdoses.


Veterinary use

Ivermectin is routinely used to control parasitic worms in the gastrointestinal tract of
ruminant Ruminants (suborder Ruminantia) are ungulate, hoofed herbivorous grazing or browsing mammals that are able to acquire nutrients from plant-based food by Enteric fermentation, fermenting it in a specialized stomach prior to digestion, principally ...
animals. These parasites normally enter the animal when it is grazing, pass the bowel, and set and mature in the intestines, after which they produce eggs that leave the animal via its droppings and can infest new pastures. Ivermectin is only effective in killing some of these parasites, this is because of an increase in anthelmintic resistance. This resistance has arisen from the persistent use of the same anthelmintic drugs for the past 40 years. In dogs, ivermectin is routinely used as prophylaxis against heartworm. Dogs with defects in the
P-glycoprotein P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein ...
gene (''MDR1''), often collie-like herding dogs, can be severely poisoned by ivermectin. The mnemonic "white feet, don't treat" refers to Scotch collies that are vulnerable to ivermectin. Some other dog breeds (especially the
Rough Collie The Rough Collie (also known as the Long-Haired Collie) is a long-coated dog breed of medium to large size that, in its original form, was a type of collie used and bred for herding sheep in Scotland. More recent breeding has focused on the Co ...
, the
Smooth Collie The Smooth Collie is a breed of dog developed originally for herding. It is a short-coated version of the Rough Collie of Lassie fame. Some breed organisations consider the smooth-coat and rough-coat dogs to be variations of the same breed. ...
, the
Shetland Sheepdog The Shetland Sheepdog, often known as the Sheltie, is a breed of herding dog that originated in the Shetland Islands of Scotland. The original name was ''Shetland Collie,'' but this caused controversy amongst Rough Collie breeders of the time, s ...
, and the
Australian Shepherd The Australian Shepherd is a breed of herding dog from the United States. The name of the breed is technically a misnomer, as it was developed in California in the 19th century; the breed was unknown in Australia at the time. It is claimed that A ...
), also have a high incidence of mutation within the ''
MDR1 P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein ...
'' gene (coding for P-glycoprotein) and are sensitive to the toxic effects of ivermectin. Clinical evidence suggests kittens are susceptible to ivermectin toxicity. A 0.01% ivermectin topical preparation for treating
ear mite Ear mites are mites that live in the ears of animals and humans. The most commonly seen species in veterinary medicine is ''Otodectes cynotis'' (Gk. ''oto''=ear, ''dectes''=biter, ''cynotis''=of the dog). This species, despite its name, is also r ...
s in cats is available. Ivermectin is sometimes used as an
acaricide Acaricides are pesticides that kill members of the arachnid subclass ''Acari'', which includes ticks and mites. Acaricides are used both in medicine and agriculture, although the desired selective toxicity differs between the two fields. Termino ...
in reptiles, both by injection and as a diluted spray. While this works well in some cases, care must be taken, as several species of reptiles are very sensitive to ivermectin. Use in turtles is particularly contraindicated. A characteristic of the antinematodal action of ivermectin is its potency: for instance, to combat ''
Dirofilaria immitis ''Dirofilaria immitis'', also known as heartworm or dog heartworm, is a parasitic roundworm that is a type of filarial worm, a small thread-like worm, that causes dirofilariasis. It is spread from host to host through the bites of mosquitoes ...
'' in dogs, ivermectin is effective at 0.001 milligram per kilogram of body weight when administered orally. For dogs, the insecticide
spinosad Spinosad is an insecticide based on chemical compounds found in the bacterial species ''Saccharopolyspora spinosa''. The genus ''Saccharopolyspora'' was discovered in 1985 in isolates from crushed sugarcane. The bacteria produce yellowish-pink ae ...
may have the effect of increasing the toxicity of ivermectin.


Pharmacology


Mechanism of action

Ivermectin and its related drugs act by interfering with the nerve and muscle functions of
helminths Parasitic worms, also known as helminths, are large macroparasites; adults can generally be seen with the naked eye. Many are intestinal worms that are soil-transmitted and infect the gastrointestinal tract. Other parasitic worms such as schi ...
and insects. The drug binds to
glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...
-gated
chloride channel Chloride channels are a superfamily of poorly understood ion channels specific for chloride. These channels may conduct many different ions, but are named for chloride because its concentration ''in vivo'' is much higher than other anions. Severa ...
s common to invertebrate nerve and muscle cells. The binding pushes the channels open, which increases the flow of chloride ions and hyper-polarizes the cell membranes, paralyzing and killing the invertebrate. Ivermectin is safe for mammals (at the normal therapeutic doses used to cure parasite infections) because mammalian glutamate-gated chloride channels only occur in the brain and spinal cord: the causative avermectins usually do not cross the
blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
, and are unlikely to bind to other mammalian ligand-gated channels.


Pharmacokinetics

Ivermectin can be given by mouth, topically, or via injection. It does not readily cross the blood–brain barrier of mammals due to the presence of
P-glycoprotein P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein ...
(the ''MDR1'' gene mutation affects the function of this protein). Crossing may still become significant if ivermectin is given at high doses, in which case brain levels peak 2–5 hours after administration. In contrast to mammals, ivermectin can cross the blood–brain barrier in tortoises, often with fatal consequences.


Chemistry

Fermentation of ''
Streptomyces avermitilis ''Streptomyces avermitilis'' is a species of bacteria in the genus ''Streptomyces''. This bacterium was discovered by Satoshi Ōmura in Shizuoka Prefecture, Japan. The first complete genome sequence of ''S. avermitilis'' was completed in 2003. ...
'' yields eight closely related
avermectin The avermectins are a series of drugs and pesticides used to treat parasitic worms and insect pests. They are a group of 16-membered macrocyclic lactone derivatives with potent anthelmintic and insecticidal properties. These naturally occurring c ...
homologues, of which B1a and B1b form the bulk of the products isolated. In a separate chemical step, the mixture is
hydrogenated Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to reduce or saturate organic co ...
to give ivermectin, which is an approximately 80:20 mixture of the two 22,23-dihydroavermectin compounds. Ivermectin is a macrocyclical lactone.


History

The
avermectin The avermectins are a series of drugs and pesticides used to treat parasitic worms and insect pests. They are a group of 16-membered macrocyclic lactone derivatives with potent anthelmintic and insecticidal properties. These naturally occurring c ...
family of compounds was discovered by
Satoshi Ōmura is a Japanese biochemist. He is known for the discovery and development of hundreds of pharmaceuticals originally occurring in microorganisms. In 2015, he was awarded the Nobel Prize in Physiology or Medicine jointly with William C. Campbell fo ...
of
Kitasato University is a private medical university headquartered in Shirokane, Minato, Tokyo, Japan. The head of the university is on the Shirokane campus, neighboring the original Kitasato Institute, the first private medical research facility in Japan which was ...
and William Campbell of
Merck Merck refers primarily to the German Merck family and three companies founded by the family, including: * the Merck Group, a German chemical, pharmaceutical and life sciences company founded in 1668 ** Merck Serono (known as EMD Serono in the Unite ...
. In 1970, Ōmura isolated a strain of ''
Streptomyces avermitilis ''Streptomyces avermitilis'' is a species of bacteria in the genus ''Streptomyces''. This bacterium was discovered by Satoshi Ōmura in Shizuoka Prefecture, Japan. The first complete genome sequence of ''S. avermitilis'' was completed in 2003. ...
'' from woodland soil near a golf course along the south east coast of
Honshu , historically called , is the largest and most populous island of Japan. It is located south of Hokkaidō across the Tsugaru Strait, north of Shikoku across the Inland Sea, and northeast of Kyūshū across the Kanmon Straits. The island separ ...
, Japan. Ōmura sent the bacteria to William Campbell, who showed that the bacterial culture could cure mice infected with the roundworm ''
Heligmosomoides polygyrus ''Heligmosomoides polygyrus'', previously named ''Nematospiroides dubius'', is a naturally occurring intestinal roundworm of rodents. It belongs to the family Trychostrongylidae, and male and female worms are morphologically distinguishable. The ...
''. Campbell isolated the active compounds from the bacterial culture, naming them "avermectins" and the bacterium ''Streptomyces avermitilis'' for the compounds' ability to clear mice of worms (in Latin: ''a'' 'without', ''vermis'' 'worms'). Of the various avermectins, Campbell's group found the compound "avermectin B1" to be the most potent when taken orally. They synthesized modified forms of avermectin B1 to improve its pharmaceutical properties, eventually choosing a mixture of at least 80% 22,23-dihydroavermectin B1a and up to 20% 22,23-dihydroavermectin B1b, a combination they called "ivermectin". The discovery of ivermectin has been described as a combination of "chance and choice." Merck was looking for a broad-spectrum anthelmintic, which ivermectin is indeed; however, Campbell noted that they "...also found a broad-spectrum agent for the control of ectoparasitic insects and mites." Merck began marketing ivermectin as a veterinary antiparasitic in 1981. By 1986, ivermectin was registered for use in 46 countries and was administered massively to cattle, sheep and other animals. By the late 1980s, ivermectin was the bestselling veterinary medicine in the world. Following its blockbuster success as a veterinary antiparasitic, another Merck scientist, Mohamed Aziz, collaborated with the World Health Organization to test the safety and efficacy of ivermectin against
onchocerciasis Onchocerciasis, also known as river blindness, is a disease caused by infection with the parasitic worm ''Onchocerca volvulus''. Symptoms include severe itching, bumps under the skin, and blindness. It is the second-most common cause of blindne ...
in humans. They found it to be highly safe and effective, triggering Merck to register ivermectin for human use as "Mectizan" in France in 1987. A year later, Merck CEO
Roy Vagelos Pindaros Roy Vagelos (born October 8, 1929, in Westfield, New Jersey), better known as P. Roy Vagelos or Roy Vagelos, is an American physician and business executive, who was president and chief executive officer (1985) and chairman (1986) of t ...
agreed that Merck would donate all ivermectin needed to eradicate river blindness. In 1998, that donation would be expanded to include ivermectin used to treat lymphatic filariasis. Ivermectin earned the title of "wonder drug" for the treatment of nematodes and arthropod parasites. Ivermectin has been used safely by hundreds of millions of people to treat river blindness and lymphatic filariasis. Half of the 2015
Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
was awarded jointly to Campbell and Ōmura for discovering avermectin, "the derivatives of which have radically lowered the incidence of
river blindness Onchocerciasis, also known as river blindness, is a disease caused by infection with the parasitic worm ''Onchocerca volvulus''. Symptoms include severe itching, bumps under the skin, and blindness. It is the second-most common cause of blindne ...
and
lymphatic filariasis Lymphatic filariasis is a human disease caused by parasitic worms known as filarial worms. Usually acquired in childhood, it is a leading cause of permanent disability worldwide. While most cases have no symptoms, some people develop a syndrome ...
, as well as showing efficacy against an expanding number of other parasitic diseases".


Society and culture


COVID-19 misinformation


Economics

The initial price proposed by Merck in 1987 was per treatment, which was unaffordable for patients who most needed ivermectin. The company donated hundreds of millions of courses of treatments since 1988 in more than 30 countries. Between 1995 and 2010, using donated ivermectin to prevent river blindness, the program is estimated to have prevented seven million years of disability at a cost of . Ivermectin is considered an inexpensive drug. As of 2019, ivermectin tablets (Stromectol) in the United States were the least expensive treatment option for lice in children at approximately , while Sklice, an ivermectin lotion, cost around for . , the
cost effectiveness Cost-effectiveness analysis (CEA) is a form of economic analysis that compares the relative costs and outcomes (effects) of different courses of action. Cost-effectiveness analysis is distinct from cost–benefit analysis, which assigns a monetar ...
of treating scabies and lice with ivermectin has not been studied.


Brand names

It is sold under the brand names Heartgard, Sklice and Stromectol in the United States, Ivomec worldwide by Merial Animal Health, Mectizan in Canada by
Merck Merck refers primarily to the German Merck family and three companies founded by the family, including: * the Merck Group, a German chemical, pharmaceutical and life sciences company founded in 1668 ** Merck Serono (known as EMD Serono in the Unite ...
, Iver-DT in Nepal by Alive Pharmaceutical and Ivexterm in Mexico by
Valeant Pharmaceuticals International Bausch Health Companies Inc. (formerly Valeant Pharmaceuticals International, Inc.) is a Canadian multinational specialty pharmaceutical company based in Laval, Quebec, Canada. It develops, manufactures and markets pharmaceutical products and ...
. In Southeast Asian countries, it is marketed by Delta Pharma Ltd. under the trade name Scabo 6. The formulation for rosacea treatment is sold under the brand name Soolantra. While in development, it was assigned the code MK-933 by Merck.


Research


Parasitic disease

Ivermectin has been researched in laboratory animals, as a potential treatment for
trichinosis Trichinosis, also known as trichinellosis, is a parasitic disease caused by roundworms of the ''Trichinella'' type. During the initial infection, invasion of the intestines can result in diarrhea, abdominal pain, and vomiting. Migration of larv ...
.


Tropical diseases

ivermectin was studied as a potential antiviral agent against
chikungunya Chikungunya is an infection caused by the ''Chikungunya virus'' (CHIKV). Symptoms include fever and joint pains. These typically occur two to twelve days after exposure. Other symptoms may include headache, muscle pain, joint swelling, and a ra ...
and
yellow fever Yellow fever is a viral disease of typically short duration. In most cases, symptoms include fever, chills, loss of appetite, nausea, muscle pains – particularly in the back – and headaches. Symptoms typically improve within five days. In ...
. In chikungunya, ivermectin showed a wide
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
safety margin as an antiviral. Ivermectin is also of interest in the prevention of
malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...
, as it is toxic to both the malaria
plasmodium ''Plasmodium'' is a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects. The life cycles of ''Plasmodium'' species involve development in a blood-feeding insect host which then injects parasites into a vert ...
itself and the
mosquito Mosquitoes (or mosquitos) are members of a group of almost 3,600 species of small flies within the family Culicidae (from the Latin ''culex'' meaning " gnat"). The word "mosquito" (formed by ''mosca'' and diminutive ''-ito'') is Spanish for "li ...
s that carry it. A direct effect on malaria parasites could not be shown in an experimental infection of volunteers with ''
Plasmodium falciparum ''Plasmodium falciparum'' is a Unicellular organism, unicellular protozoan parasite of humans, and the deadliest species of ''Plasmodium'' that causes malaria in humans. The parasite is transmitted through the bite of a female ''Anopheles'' mosqu ...
''. Use of ivermectin at higher doses necessary to control malaria is probably safe, though large clinical trials have not yet been done to definitively establish the efficacy or safety of ivermectin for prophylaxis or treatment of malaria. Mass drug administration of a population with ivermectin to treat and prevent nematode infestation is effective for eliminating malaria-bearing mosquitos and thereby reducing infection with residual
malaria parasites ''Plasmodium'' is a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects. The life cycles of ''Plasmodium'' species involve development in a blood-feeding insect host which then injects parasites into a verte ...
. One alternative to ivermectin is
moxidectin Moxidectin is an anthelmintic drug used in animals to prevent or control parasitic worms (helminths), such as heartworm and intestinal worms, in dogs, cats, horses, cattle and sheep. Moxidectin kills some of the most common internal and external ...
, which has been approved by the Food and Drug Administration for use in people with river blindness. Moxidectin has a longer half-life than ivermectin and may eventually supplant ivermectin as it is a more potent microfilaricide, but there is a need for additional clinical trials, with long-term follow-up, to assess whether moxidectin is safe and effective for treatment of nematode infection in children and women of childbearing potential. There is tentative evidence that ivermectin kills bedbugs, as part of
integrated pest management Integrated pest management (IPM), also known as integrated pest control (IPC) is a broad-based approach that integrates both chemical and non-chemical practices for economic control of pests. IPM aims to suppress pest populations below the econ ...
for bedbug infestations. However, such use may require a prolonged course of treatment which is of unclear safety.


NAFLD

In 2013, ivermectin was demonstrated as a novel ligand of the farnesoid X receptor, a therapeutic target for
nonalcoholic fatty liver disease Non-alcoholic fatty liver disease (NAFLD), also known as metabolic (dysfunction) associated fatty liver disease (MAFLD), is excessive fat build-up in the liver without another clear cause such as alcohol use. There are two types; non-alcoholic ...
.


COVID-19

During the COVID-19 pandemic, ivermectin was researched for possible utility in preventing and treating COVID-19, but no good evidence of benefit was found.


See also

*
Bioprospecting Bioprospecting (also known as biodiversity prospecting) is the exploration of natural sources for small molecules, macromolecules and biochemical and genetic information that could be developed into commercialization, commercially valuable prod ...
*
Carter Center The Carter Center is a nongovernmental, not-for-profit organization founded in 1982 by former U.S. President Jimmy Carter. He and his wife Rosalynn Carter partnered with Emory University just after his defeat in the 1980 United States presidenti ...
* Horse management#Parasite control * Neglected diseases * United Front Against Riverblindness


Notes


References


External links

*
The Carter Center River Blindness (Onchocerciasis) Control Program
* * {{Authority control Acaricides Antiparasitic agents GABAA receptor positive allosteric modulators Glycine receptor agonists Insecticides Japanese inventions Macrolides Merck & Co. brands Nicotinic agonists Peripherally selective drugs Veterinary drugs World Health Organization essential medicines Chloride channel openers Wikipedia medicine articles ready to translate